An exon splice enhancer mutation causes autosomal dominant GH deficiency.
J Clin Endocrinol Metab
; 87(2): 847-52, 2002 Feb.
Article
en En
| MEDLINE
| ID: mdl-11836331
Familial isolated GH deficiency type II (IGHD II) is caused, in some cases, by heterogeneous IVS3 mutations that affect GH mRNA splicing. We report here our finding an A-->G transition of the fifth base of exon 3 (E3+ 5 A-->G) in affected individuals from an IGHD II family. This mutation disrupts a (GAA)(n) exon splice enhancer (ESE) motif immediately following the weak IVS2 3' splice site. The mutation also destroys an MboII site used to demonstrate heterozygosity in all affected family members. To determine the effect of ESE mutations on GH mRNA processing, GH(3) cells were transfected with expression constructs containing the normal ESE, +5 A-->G, or other ESE mutations, and cDNAs derived from the resulting GH mRNAs were sequenced. All ESE mutations studied reduced activation of the IVS2 3' splice site and caused either partial E3 skipping, due to activation of an E3+ 45 cryptic 3' splice site, or complete E3 skipping. Partial or complete E3 skipping led to loss of the codons for amino acids 32-46 or 32-71, respectively, of the mature GH protein. Our data indicate that the E3+ 5 A-->G mutation causes IGHD II because it perturbs an ESE required for GH splicing.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Empalme del ARN
/
Exones
/
Elementos de Facilitación Genéticos
/
Mutación Puntual
/
Hormona de Crecimiento Humana
/
Genes Dominantes
Tipo de estudio:
Etiology_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos